Discovery of novel steroidal histamine H3 receptor antagonists/inverse agonists.
Bioorg Med Chem Lett
; 27(19): 4525-4530, 2017 10 01.
Article
in En
| MEDLINE
| ID: mdl-28888822
ABSTRACT
Emerging from an HTS campaign, novel steroid-based histamine H3 receptor antagonists were identified and characterized. Structural moieties of the hit compounds were combined to improve binding affinities which resulted in compound 4 as lead molecule. During the lead optimization due to the versatile modifications of diamino steroid derivatives, several in vitro potent compounds with subnanomolar binding affinities to histamine H3 receptors were found. The unfavorable binding to rat muscarinic receptors was successfully reduced by tuning the basicity. Compound 20 showed significant in vivo activity in the rat dipsogenia model and could serve as a pharmacological tool in the future.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Histamine Agonists
/
Receptors, Histamine H3
/
Histamine H3 Antagonists
/
Drug Discovery
Limits:
Animals
/
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2017
Document type:
Article